- Email: [email protected]
Cycloadditions of NS functions to cyclopentadienones
TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 6709–6711
Pergamon
Cycloadditions of NS functions to cyclopentadienones Hadjila Chabane,a Otto Meth-Cohn,a,* Charles W. Rees,b,* Andrew J. P. Whiteb and David J. Williamsb a
Chemistry Department, University of Sunderland, Sunderland SR1 3SD, UK b Chemistry Department, Imperial College London, London SW7 2AZ, UK Received 2 June 2003; revised 20 June 2003; accepted 27 June 2003
Abstract—Cyclopentadienones react with EtO2CNSO and related NS reagents to provide ready syntheses of 1,2,5-thiadiazolidines (8, 12, 17), diaminosulfanes (11, 13), an aminocyclopentenone (10) and the first unoxidised 1,2,3-oxathiazolidine (16), all in a mechanistically rational manner. © 2003 Elsevier Ltd. All rights reserved.
Tetracyclone 1 is the classic reagent for the interception of transient dienophiles, and cyclopentadienones are widely used 4p components in Diels–Alder reactions.1 However, almost nothing is known of their reactions with NS containing dienophiles which are known to react effectively with enes and dienes.2 Tetracyclone is converted into tetraphenylpyrid-2-one 7 by warming with trithiazyl trichloride (NSCl)3, which dissociates into the monomeric thiazyl chloride, NSCl, a highly reactive dienophile;3 this transformation is achieved quantitatively and much more conveniently4 if the NSCl is generated in situ from urethane, thionyl chloride and pyridine—the highly effective Katz reagent.5,6 We now report a diverse range of reactions of some representative cyclopentadienones 1, 9 and 15 with Katz reagent, which involves the intermediates 2, 3 and 4 (Scheme 1), and with preformed EtO2CNSO 2 and the closely related N,N%-bis(ethoxycarbonyl) sulfur diimide, EtO2CNSNCO2Et (5).
Scheme 1. * Corresponding authors. 0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0040-4039(03)01646-0
With Katz reagent in boiling benzene (12 h) tetracyclone 1 gave the pyrid-2-yl carbonate 6 (31%) and thence the pyridone 7 (37%) but in boiling toluene (12 h) it gave 7 quantitatively. However, if the urethane was replaced by EtO2CNSO 2, 1 was rapidly converted into 7 (86%) in 3 h at room temperature (rt). There was no reaction with 2 in the absence of thionyl chloride and pyridine even on prolonged heating in toluene, but on addition of pyridine (which catalyses the conversion of 2 into the sulfur diimide 57) the pyridone 7 is again formed together with a low yield of the formal [3+2] cycloadduct 8 of 1 and 5. A much higher yield of 8 (81%) was formed directly from 5 in boiling toluene (12 h) and its structure was confirmed by X-ray crystallography.8 Tetracyclone 1 is thus converted into the pyridone under acidic conditions (SOCl2), and into the cycloadduct 8 under neutral conditions, both in high yield (Scheme 2). None of the analogous pyridones were formed from the dimethyldiphenyl-cyclopentadienones 9 and 15. The 3,4-dimethyl compound 9 (Scheme 3) reacted slowly with Katz reagent at rt to give a product shown (Fig. 1) by X-ray crystallography8,9 to be the primary amine 10 (17%); this yield was increased to 54% by slowly adding SOCl2 to a mixture of all the other reactants. An extra equivalent of urethane was added to the Katz mixture in the hope of generating the sulfur diimide 5 in situ, and this mixture reacted with 9 at rt to give a minor red oil 11 and a major colourless oil 12. The cyclopentadienone structure of 11 was confirmed by X-ray crystallography8 of 13 (Fig. 2), its Diels–Alder adduct with DMAD (Scheme 3). The pattern of bond-
6710
H. Chabane et al. / Tetrahedron Letters 44 (2003) 6709–6711
Product 12 is a formal [3+2] adduct of 9 and 5, and the minor product was traced to the acid-catalysed conversion of 9 into the small amount of the non-antiaromatic isomer 14 with an exocyclic methylene group. Pure 14 gave the new cyclopentadienone 11 as the sole product in up to 34% with all three NS reagents. Preformed sulfur diimide 5 converted 9 into the cycloadduct 12 in high yield (79%) at rt in toluene; only a trace of 11 was found since there was very little tautomerism of 9 under these neutral conditions.
Scheme 2.
The 2,5-dimethyl analogue 15 exists as its Diels–Alder dimer at rt and does not react with NS reagents until heated. The Katz mixture gave the formal [3+2] adduct 16 of 15 with EtO2CNSO 2 at 70°C (35%) and the same product was formed in higher yield (74%) by brief (15 min) heating of neat 15 and 2 at 130°C. The sulfur diimide 5, from Katz reagent with extra urethane, gave the corresponding adduct 17 (65%) (Scheme 4). We now suggest a rational and unifying mechanistic scheme which accounts for these diverse products. Following Weinreb and Kresze’s detailed studies of simpler dienes with NS reagents,2 we propose that the reactions all start by [4+2] cycloaddition of the 4p donor cyclopentadienones with EtO2CNS+X where XO−, OSOCl, Cl and EtO2CN−; electrophilic catalysts are represented by protons. The fate of the [4+2] adduct 18 (Scheme 5) depends critically upon its substituents and
Scheme 3. Figure 2. The molecular structure of 13.
Figure 1. The molecular structure of 10.
ing within the –CH2N(CO2R)SN(CO2R)-fragment is very similar to that observed in the only other structurally characterised example of a molecule containing this unusual fragment, dimethyl N,N%-(thio-bis(methyliminocarbonyloxy))-bis(ethanimidothiolate).10
Scheme 4.
H. Chabane et al. / Tetrahedron Letters 44 (2003) 6709–6711
6711
611 and finally gives pyridone 7. In contrast, the two dimethylcyclopentadienones 9 and 15 gave no pyridones, possibly because of reduced stability of the key carbonium ions analogous to 20; furthermore the presence of a methyl group provides a lower energy pathway for the conversion of 9 into the amine 10 (Scheme 6). The methylene isomer 14 of 9 is well set up to undergo an ene reaction to give the bisaminosulfane 11 (Scheme 6). The [4+2] cycloaddition—2,3-sigmatropic rearrangement sequence (Scheme 5) in the reaction of the 2,5-dimethyl analogue 15 with 2 and 5 leads to the observed adducts 16 and 17 (Scheme 4). Thus we have shown that the readily available cyclopentadienones react with some NS reagents, also readily available, to provide useful syntheses of some new and rare structures. These are 1,2,5-thiadiazolidines and imidazolones derived therefrom, pyridones, diaminosulfanes, an aminocyclopentenone, and the first unoxidised 1,2,3-oxathiazolidine 16,12 and a mechanistic framework is proposed to account for their formation.
Scheme 5.
Scheme 6.
on the electrophilicity of the dienophile and the medium. In the absence of electrophiles such as thionyl chloride the initial adducts undergo a thermal 2,3-sigmatropic rearrangement (arrows in 18) to give the formal [3+2] adducts 8, 12, 16 and 17. With tetracyclone 1 in the presence of SOCl2 and pyridine, the adduct 18 can undergo a faster acid-catalysed rearrangement (1920) via a stabilised 1,3-diphenylallylic carbonium ion 20, to give N-ethoxcarbonylpyridone 21 which rearranges to
References 1. Ogliaruso, M. A.; Romanelli, M. G.; Becker, E. I. Chem. Rev. 1965, 65, 261–367. 2. (a) Garigipati, R. S.; Freyer, A. J.; Whittle, R. R.; Weinreb, S. M. J. Am. Chem. Soc. 1984, 106, 7861–7867; (b) Natsugari, H.; Whittle, R. R.; Weinreb, S. M. J. Am. Chem. Soc. 1984, 106, 7867–7872; (c) Bussas, R.; Kresze, G. Liebigs Ann. Chem. 1982, 545–563. 3. Duan, X.-L.; Perrins, R.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1 1997, 1617–1622. 4. Laaman, S. M.; Meth-Cohn, O.; Rees, C. W. Arkivoc 2002, ii, 90–94. 5. Shi, S.; Katz, T. J.; Young, B. V.; Liu, L. J. Org. Chem. 1995, 60, 1285–1297. 6. Laaman, S. M.; Meth-Cohn, O.; Rees, C. W. Synthesis 1999, 757–759. 7. Smyth, T. P.; O’Donnell, M. E.; O’Connor, M. J.; St. Ledger, J. O. J. Org. Chem. 1998, 63, 7600–7618. 8. Crystallographic data (excluding structure factors) for the structures in this paper, have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 198788 to 198790. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44(0)-1223-336033 or e-mail: [email protected]). 9. Compound 10 exhibits spontaneous resolution upon crystallisation, though the absolute chirality of the molecules in the crystal studied could not be determined from the X-ray data. 10. Ammon, H. L.; Seymour, R. J.; Huffman, W. M.; D’Silva, T. D. J. Acta Crystallogr., Sect. C 1995, 51, 1619–1621. 11. (a) McKillop, A.; Zelesko, M. J.; Taylor, E. C. Tetrahedron Lett. 1968, 4945–4948; (b) Afarinkia, K.; Mahmood, F. Tetrahedron Lett. 1998, 39, 493–496. 12. Examples of the S-oxides and -dioxides are known, e.g.: Posakony, J. J.; Grierson, J. R.; Tewson, T. J. J. Org. Chem. 2002, 67, 5164–5169.
Pergamon
Cycloadditions of NS functions to cyclopentadienones Hadjila Chabane,a Otto Meth-Cohn,a,* Charles W. Rees,b,* Andrew J. P. Whiteb and David J. Williamsb a
Chemistry Department, University of Sunderland, Sunderland SR1 3SD, UK b Chemistry Department, Imperial College London, London SW7 2AZ, UK Received 2 June 2003; revised 20 June 2003; accepted 27 June 2003
Abstract—Cyclopentadienones react with EtO2CNSO and related NS reagents to provide ready syntheses of 1,2,5-thiadiazolidines (8, 12, 17), diaminosulfanes (11, 13), an aminocyclopentenone (10) and the first unoxidised 1,2,3-oxathiazolidine (16), all in a mechanistically rational manner. © 2003 Elsevier Ltd. All rights reserved.
Tetracyclone 1 is the classic reagent for the interception of transient dienophiles, and cyclopentadienones are widely used 4p components in Diels–Alder reactions.1 However, almost nothing is known of their reactions with NS containing dienophiles which are known to react effectively with enes and dienes.2 Tetracyclone is converted into tetraphenylpyrid-2-one 7 by warming with trithiazyl trichloride (NSCl)3, which dissociates into the monomeric thiazyl chloride, NSCl, a highly reactive dienophile;3 this transformation is achieved quantitatively and much more conveniently4 if the NSCl is generated in situ from urethane, thionyl chloride and pyridine—the highly effective Katz reagent.5,6 We now report a diverse range of reactions of some representative cyclopentadienones 1, 9 and 15 with Katz reagent, which involves the intermediates 2, 3 and 4 (Scheme 1), and with preformed EtO2CNSO 2 and the closely related N,N%-bis(ethoxycarbonyl) sulfur diimide, EtO2CNSNCO2Et (5).
Scheme 1. * Corresponding authors. 0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0040-4039(03)01646-0
With Katz reagent in boiling benzene (12 h) tetracyclone 1 gave the pyrid-2-yl carbonate 6 (31%) and thence the pyridone 7 (37%) but in boiling toluene (12 h) it gave 7 quantitatively. However, if the urethane was replaced by EtO2CNSO 2, 1 was rapidly converted into 7 (86%) in 3 h at room temperature (rt). There was no reaction with 2 in the absence of thionyl chloride and pyridine even on prolonged heating in toluene, but on addition of pyridine (which catalyses the conversion of 2 into the sulfur diimide 57) the pyridone 7 is again formed together with a low yield of the formal [3+2] cycloadduct 8 of 1 and 5. A much higher yield of 8 (81%) was formed directly from 5 in boiling toluene (12 h) and its structure was confirmed by X-ray crystallography.8 Tetracyclone 1 is thus converted into the pyridone under acidic conditions (SOCl2), and into the cycloadduct 8 under neutral conditions, both in high yield (Scheme 2). None of the analogous pyridones were formed from the dimethyldiphenyl-cyclopentadienones 9 and 15. The 3,4-dimethyl compound 9 (Scheme 3) reacted slowly with Katz reagent at rt to give a product shown (Fig. 1) by X-ray crystallography8,9 to be the primary amine 10 (17%); this yield was increased to 54% by slowly adding SOCl2 to a mixture of all the other reactants. An extra equivalent of urethane was added to the Katz mixture in the hope of generating the sulfur diimide 5 in situ, and this mixture reacted with 9 at rt to give a minor red oil 11 and a major colourless oil 12. The cyclopentadienone structure of 11 was confirmed by X-ray crystallography8 of 13 (Fig. 2), its Diels–Alder adduct with DMAD (Scheme 3). The pattern of bond-
6710
H. Chabane et al. / Tetrahedron Letters 44 (2003) 6709–6711
Product 12 is a formal [3+2] adduct of 9 and 5, and the minor product was traced to the acid-catalysed conversion of 9 into the small amount of the non-antiaromatic isomer 14 with an exocyclic methylene group. Pure 14 gave the new cyclopentadienone 11 as the sole product in up to 34% with all three NS reagents. Preformed sulfur diimide 5 converted 9 into the cycloadduct 12 in high yield (79%) at rt in toluene; only a trace of 11 was found since there was very little tautomerism of 9 under these neutral conditions.
Scheme 2.
The 2,5-dimethyl analogue 15 exists as its Diels–Alder dimer at rt and does not react with NS reagents until heated. The Katz mixture gave the formal [3+2] adduct 16 of 15 with EtO2CNSO 2 at 70°C (35%) and the same product was formed in higher yield (74%) by brief (15 min) heating of neat 15 and 2 at 130°C. The sulfur diimide 5, from Katz reagent with extra urethane, gave the corresponding adduct 17 (65%) (Scheme 4). We now suggest a rational and unifying mechanistic scheme which accounts for these diverse products. Following Weinreb and Kresze’s detailed studies of simpler dienes with NS reagents,2 we propose that the reactions all start by [4+2] cycloaddition of the 4p donor cyclopentadienones with EtO2CNS+X where XO−, OSOCl, Cl and EtO2CN−; electrophilic catalysts are represented by protons. The fate of the [4+2] adduct 18 (Scheme 5) depends critically upon its substituents and
Scheme 3. Figure 2. The molecular structure of 13.
Figure 1. The molecular structure of 10.
ing within the –CH2N(CO2R)SN(CO2R)-fragment is very similar to that observed in the only other structurally characterised example of a molecule containing this unusual fragment, dimethyl N,N%-(thio-bis(methyliminocarbonyloxy))-bis(ethanimidothiolate).10
Scheme 4.
H. Chabane et al. / Tetrahedron Letters 44 (2003) 6709–6711
6711
611 and finally gives pyridone 7. In contrast, the two dimethylcyclopentadienones 9 and 15 gave no pyridones, possibly because of reduced stability of the key carbonium ions analogous to 20; furthermore the presence of a methyl group provides a lower energy pathway for the conversion of 9 into the amine 10 (Scheme 6). The methylene isomer 14 of 9 is well set up to undergo an ene reaction to give the bisaminosulfane 11 (Scheme 6). The [4+2] cycloaddition—2,3-sigmatropic rearrangement sequence (Scheme 5) in the reaction of the 2,5-dimethyl analogue 15 with 2 and 5 leads to the observed adducts 16 and 17 (Scheme 4). Thus we have shown that the readily available cyclopentadienones react with some NS reagents, also readily available, to provide useful syntheses of some new and rare structures. These are 1,2,5-thiadiazolidines and imidazolones derived therefrom, pyridones, diaminosulfanes, an aminocyclopentenone, and the first unoxidised 1,2,3-oxathiazolidine 16,12 and a mechanistic framework is proposed to account for their formation.
Scheme 5.
Scheme 6.
on the electrophilicity of the dienophile and the medium. In the absence of electrophiles such as thionyl chloride the initial adducts undergo a thermal 2,3-sigmatropic rearrangement (arrows in 18) to give the formal [3+2] adducts 8, 12, 16 and 17. With tetracyclone 1 in the presence of SOCl2 and pyridine, the adduct 18 can undergo a faster acid-catalysed rearrangement (1920) via a stabilised 1,3-diphenylallylic carbonium ion 20, to give N-ethoxcarbonylpyridone 21 which rearranges to
References 1. Ogliaruso, M. A.; Romanelli, M. G.; Becker, E. I. Chem. Rev. 1965, 65, 261–367. 2. (a) Garigipati, R. S.; Freyer, A. J.; Whittle, R. R.; Weinreb, S. M. J. Am. Chem. Soc. 1984, 106, 7861–7867; (b) Natsugari, H.; Whittle, R. R.; Weinreb, S. M. J. Am. Chem. Soc. 1984, 106, 7867–7872; (c) Bussas, R.; Kresze, G. Liebigs Ann. Chem. 1982, 545–563. 3. Duan, X.-L.; Perrins, R.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1 1997, 1617–1622. 4. Laaman, S. M.; Meth-Cohn, O.; Rees, C. W. Arkivoc 2002, ii, 90–94. 5. Shi, S.; Katz, T. J.; Young, B. V.; Liu, L. J. Org. Chem. 1995, 60, 1285–1297. 6. Laaman, S. M.; Meth-Cohn, O.; Rees, C. W. Synthesis 1999, 757–759. 7. Smyth, T. P.; O’Donnell, M. E.; O’Connor, M. J.; St. Ledger, J. O. J. Org. Chem. 1998, 63, 7600–7618. 8. Crystallographic data (excluding structure factors) for the structures in this paper, have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 198788 to 198790. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44(0)-1223-336033 or e-mail: [email protected]). 9. Compound 10 exhibits spontaneous resolution upon crystallisation, though the absolute chirality of the molecules in the crystal studied could not be determined from the X-ray data. 10. Ammon, H. L.; Seymour, R. J.; Huffman, W. M.; D’Silva, T. D. J. Acta Crystallogr., Sect. C 1995, 51, 1619–1621. 11. (a) McKillop, A.; Zelesko, M. J.; Taylor, E. C. Tetrahedron Lett. 1968, 4945–4948; (b) Afarinkia, K.; Mahmood, F. Tetrahedron Lett. 1998, 39, 493–496. 12. Examples of the S-oxides and -dioxides are known, e.g.: Posakony, J. J.; Grierson, J. R.; Tewson, T. J. J. Org. Chem. 2002, 67, 5164–5169.